PUBLICATION

Endocytic trafficking factor VPS45 is essential for spatial regulation of lens fiber differentiation in zebrafish

Authors
Mochizuki, T., Kojima, Y., Nishiwaki, Y., Harakuni, T., Masai, I.
ID
ZDB-PUB-181017-4
Date
2018
Source
Development (Cambridge, England)   145(20): (Journal)
Registered Authors
Harakuni, Tetsuya, Kojima, Yutaka, Masai, Ichiro, Mochizuki, Toshiaki, Nishiwaki, Yuko
Keywords
Endocytic trafficking, Lens fiber differentiation, VPS45, Zebrafish
MeSH Terms
  • Animals
  • Cell Differentiation*
  • Endocytosis*
  • Epithelium/metabolism
  • Fibroblast Growth Factors/metabolism
  • Integrin beta1/metabolism
  • Lens, Crystalline/cytology*
  • Lens, Crystalline/metabolism*
  • Mutation/genetics
  • Phenotype
  • Protein Transport
  • Transforming Growth Factor beta/metabolism
  • Vesicular Transport Proteins/genetics
  • Vesicular Transport Proteins/metabolism*
  • Wnt Signaling Pathway
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
30322969 Full text @ Development
Abstract
In vertebrate lens, lens epithelial cells cover the anterior half of the lens fiber core. Lens epithelial cells proliferate, move posteriorly and start to differentiate into lens fiber cells at the lens equator. Although FGF signaling promotes this equatorial commencement of lens fiber differentiation, the underlying mechanism is not fully understood. Here, we show that lens epithelial cells abnormally enter lens fiber differentiation without passing through the equator in zebrafish vps45 mutants. VPS45 belongs to the Sec1/Munc18-like protein family and promotes endosome trafficking, which differentially modulates signal transduction. Ectopic lens fiber differentiation in vps45 mutants does not depend on FGF, but is mediated through activation of TGFβ signaling and inhibition of canonical Wnt signaling. Thus, VPS45 normally suppresses lens fiber differentiation in the anterior region of lens epithelium by modulating TGFβ and canonical Wnt signaling pathways. These data indicate a novel role of endosome trafficking to ensure equator-dependent commencement of lens fiber differentiation.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping